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IL-17RE is an orphan receptor of the IL-17 receptor family. Qian and colleagues identify IL-17RE as the receptor specific for IL-17C signaling in mucosal defense against intestinal pathogens. Interleukin 17 receptor E (IL-17RE) is an orphan receptor of the IL-17 receptor family. Here we show that IL-17RE is a receptor specific to IL-17C and has an essential role in host mucosal defense against infection. IL-17C activated downstream signaling through IL-17RE–IL-17RA complex for the induction of genes encoding antibacterial peptides as well as proinflammatory molecules. IL-17C was upregulated in colon epithelial cells during infection with Citrobacter rodentium and acted in synergy with IL-22 to induce the expression of antibacterial peptides in colon epithelial cells. Loss of IL-17C-mediated signaling in IL-17RE-deficient mice led to lower expression of genes encoding antibacterial molecules, greater bacterial burden and early mortality during infection. Together our data identify IL-17RE as a receptor of IL-17C that regulates early innate immunity to intestinal pathogens.

The Juno spacecraft, which is in a polar orbit around Jupiter, is providing direct measurements of the planet’s magnetic field close to its surface 1 . A recent analysis of observations of Jupiter’s magnetic field from eight (of the first nine) Juno orbits has provided a spherical-harmonic reference model (JRM09) 2 of Jupiter’s magnetic field outside the planet. This model is of particular interest for understanding processes in Jupiter’s magnetosphere, but to study the field within the planet and thus the dynamo mechanism that is responsible for generating Jupiter’s main magnetic field, alternative models are preferred. Here we report maps of the magnetic field at a range of depths within Jupiter. We find that Jupiter’s magnetic field is different from all other known planetary magnetic fields. Within Jupiter, most of the flux emerges from the dynamo region in a narrow band in the northern hemisphere, some of which returns through an intense, isolated flux patch near the equator. Elsewhere, the field is much weaker. The non-dipolar part of the field is confined almost entirely to the northern hemisphere, so there the field is strongly non-dipolar and in the southern hemisphere it is predominantly dipolar. We suggest that Jupiter’s dynamo, unlike Earth’s, does not operate in a thick, homogeneous shell, and we propose that this unexpected field morphology arises from radial variations, possibly including layering, in density or electrical conductivity, or both. Maps of Jupiter’s internal magnetic field at a range of depths reveal an unusual morphology, suggesting that Jupiter’s dynamo, unlike Earth’s, does not operate in a thick, homogeneous shell.

Despite the recent clinical success of T cell checkpoint inhibition targeting the CTLA-4 and PD-1 pathways, many patients either fail to achieve objective responses or they develop resistance to therapy. In some cases, poor responses to checkpoint blockade have been linked to suboptimal CD28 costimulation and the inability to generate and maintain a productive adaptive anti-tumor immune response. To address this, here we utilize directed evolution to engineer a CD80 IgV domain with increased PD-L1 affinity and fuse this to an immunoglobulin Fc domain, creating a therapeutic (ALPN-202, davoceticept) capable of providing CD28 costimulation in a PD-L1-dependent fashion while also antagonizing PD-1 - PD-L1 and CTLA-4–CD80/CD86 interactions. We demonstrate that by combining CD28 costimulation and dual checkpoint inhibition, ALPN-202 enhances T cell activation and anti-tumor efficacy in cell-based assays and mouse tumor models more potently than checkpoint blockade alone and thus has the potential to generate potent, clinically meaningful anti-tumor immunity in humans. CD28 costimulatory signalling can be suppressed by immune checkpoints, such as CTLA-4 and PD-1. Here the authors describe the design of the fusion therapeutic davoceticept (ALPN-202), based on a variant CD80 extracellular domain engineered to bind PD-L1 as well as CD28 and CTLA-4, providing direct T cell costimulation and dual checkpoint inhibition to enable anti-tumor immune responses.

Oxygen is the most common element after hydrogen and helium in Jupiter’s atmosphere, and may have been the primary condensable (as water ice) in the protoplanetary disk. Prior to the Juno mission, in situ measurements of Jupiter’s water abundance were obtained from the Galileo probe, which dropped into a meteorologically anomalous site. The findings of the Galileo probe were inconclusive because the concentration of water was still increasing when the probe ceased sending data. Here we report on the water abundance in the equatorial region (0 to 4 degrees north latitude), based on data taken at 1.25 to 22 GHz from the Juno microwave radiometer, probing pressures of approximately 0.7 to 30 bar. Because Juno discovered the deep atmosphere to be surprisingly variable as a function of latitude, it remains to confirm whether the equatorial abundance represents Jupiter’s global water abundance. The water abundance at the equatorial region is inferred to be 2 . 5 − 1.6 + 2.2 × 1 0 3 ppm, or 2 . 7 − 1.7 + 2.4 times the elemental ratio of protosolar oxygen to hydrogen (1 σ uncertainties). If this reflects the global water abundance, the result suggests that the planetesimals that formed Jupiter were unlikely to have been water-rich clathrate hydrates. Juno’s microwave radiometer data could measure the water concentration in the deep atmosphere of Jupiter (0.7 to 30 bar) at the equator: 2 . 7 − 1.7 + 2.4 times the solar O/H abundance, with a thermal vertical structure compatible with a moist adiabat.

This paper presents an analysis of Juno's first radio occultation experiments. Relying on two‐way radio links in the X‐ and Ka‐bands, we processed data from NASA's Deep Space Network antennas through a ray‐tracing inversion algorithm. By effectively isolating dispersive effects, we obtained measurements of the neutral atmosphere's characteristics. This enabled the derivation of pressure and temperature profiles from the recorded frequencies. These results complement prior data from Voyager occultations and CIRS observations, providing valuable contributions to our understanding of Jupiter's atmospheric dynamics.

The upper layers of Jupiter's atmosphere, offering critical insights into the planet's deeper structure, are accessible through radio occultation experiments. Since July 2023, NASA's Juno extended mission has provided the first high‐resolution radio occultation measurements since the Voyager era, probing the thermal structure and composition down to approximately 0.5 bar. We use these measurements to study Jupiter's latitudinally dependent vertical thermal structure. We observe cooler stratospheric and warmer tropospheric temperatures at the equatorial region compared to mid‐ and high‐latitudes, and temporal variations in the North Equatorial Belt's thermal structure on a time scale of a few months. These observations align with archival mid‐infrared data from Cassini's CIRS and current ground‐based Texas Echelon Cross Echelle Spectrograph observations, as well as previous studies based on Voyager radio occultations and the Galileo probe, offering an enhanced view of Jupiter's lower stratosphere and upper troposphere thermal structure.

Lightning flashes have been observed by a number of missions that visited or flew by Jupiter over the past several decades. Imagery led to a flash rate estimate of about 4 × 10 −3 flashes per square kilometre per year (refs. 1 , 2 ). The spatial extent of Voyager flashes was estimated to be about 30 kilometres (half-width at half-maximum intensity, HWHM), but the camera was unlikely to have detected the dim outer edges of the flashes, given its weak response to the brightest spectral line of Jovian lightning emission, the 656.3-nanometre Hα line of atomic hydrogen 1 , 3 – 6 . The spatial resolution of some cameras allowed investigators to confirm 22 flashes with HWHM greater than 42 kilometres, and to estimate one with an HWHM of 37 to 45 kilometres (refs. 1 , 7 – 9 ). These flashes, with optical energies comparable to terrestrial ‘superbolts’—of (0.02–1.6) × 10 10  joules—have been interpreted as tracers of moist convection originating near the 5-bar level of Jupiter’s atmosphere (assuming photon scattering from points beneath the clouds) 1 – 3 , 7 , 8 , 10 – 12 . Previous observations of lightning have been limited by camera sensitivity, distance from Jupiter and long exposures (about 680 milliseconds to 85 seconds), meaning that some measurements were probably superimposed flashes reported as one 1 , 2 , 7 , 9 , 10 , 13 . Here we report optical observations of lightning flashes by the Juno spacecraft with energies of approximately 10 5 –10 8  joules, flash durations as short as 5.4 milliseconds and inter-flash separations of tens of milliseconds, with typical terrestrial energies. The flash rate is about 6.1 × 10 −2 flashes per square kilometre per year, more than an order of magnitude greater than hitherto seen. Several flashes are of such small spatial extent that they must originate above the 2-bar level, where there is no liquid water 14 , 15 . This implies that multiple mechanisms for generating lightning on Jupiter need to be considered for a full understanding of the planet’s atmospheric convection and composition. Small lightning flashes detected on Jupiter by Juno have shallow origins above the 2-bar level of Jupiter’s atmosphere where temperatures are too low for liquid water to exist.

Juno's microwave radiometer experiment (MWR) provided the first spatially resolved observations beneath the surface of Ganymede's ice shell. The results indicate that scattering is a significant component of the observed brightness temperature, which is a combination of the upwelling ice emission and reflected emission from the sky and from Jupiter's synchrotron emission (Brown et al., 2023). Retrieval of the sub‐surface ice temperature profile requires that these confounding signals are estimated and removed to isolate the thermal signature of the ice. We present data analysis and model results to estimate the reflected synchrotron emission component. Our results indicate reflected emission over a broad range of observed angles, due to surface roughness and internal scattering. Based on viewing geometry, direct specular reflection from a smooth surface at a narrow angle is not observed. A microwave‐reflective medium is indicated, that is, a very rough surface and/or non‐homogeneous subsurface. Plain Language Summary On 7 June 2021, Juno had a close flyby of Jupiter's moon Ganymede, flying approximately 1,000 km above the surface. During the flyby, Juno's six channel Microwave Radiometer (MWR) mapped a portion of Ganymede, providing the first resolved observations of Ganymede's sub‐surface ice shell. The observed brightness temperature is composed of upwelling thermal emission from the ice shell and reflected radiation from the sky and from Jupiter's synchrotron emission. To study the sub‐surface ice shell temperature profile, we present data analysis and model results to estimate the reflected radiation component. The radiation is reflected diffusively by a very rough surface and/or non‐homogeneous subsurface. Key Points Reflected radiation from the sky and from Jupiter's synchrotron is an important component for Juno microwave radiometer experiment (MWR) observations at 0.6 and 1.2 GHz Absence of specular reflection indicating that Ganymede has a rough surface Reflections originate mostly from internal scattering

The heterodimeric cytokine IL-27 consists of the subunits p28 and EBI3. Hunter and colleagues demonstrate that p28 acting alone can inhibit the signaling of many cytokines by interfering with the common receptor gp130. The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique functions. Here we show that IL-27p28, independently of EBI3, antagonized cytokine signaling through gp130 and IL-6-mediated production of IL-17 and IL-10. Similarly, the ability to generate antibody responses was dependent on the activity of gp130-signaling cytokines. Mice transgenic for expression of IL-27p28 showed a substantial defect in the formation of germinal centers and antibody production. Thus, IL-27p28, as a natural antagonist of gp130-mediated signaling, may be useful as a therapeutic for managing inflammation mediated by cytokines that signal through gp130.

Intense electromagnetic impulses induced by Jupiter’s lightning have been recognised to produce both low-frequency dispersed whistler emissions and non-dispersed radio pulses. Here we report the discovery of electromagnetic pulses associated with Jovian lightning. Detected by the Juno Waves instrument during its polar perijove passes, the dispersed millisecond pulses called Jupiter dispersed pulses (JDPs) provide evidence of low density holes in Jupiter’s ionosphere. 445 of these JDP emissions have been observed in snapshots of electric field waveforms. Assuming that the maximum delay occurs in the vicinity of the free space ordinary mode cutoff frequency, we estimate the characteristic plasma densities (5.1 to 250 cm −3 ) and lengths (0.6 km to 1.3 × 10 5  km) of plasma irregularities along the line of propagation from lightning to Juno. These irregularities show a direct link to low plasma density holes with ≤250 cm −3 in the nightside ionosphere. Intense electromagnetic impulses induced by Jupiter’s lightning can produce both low-frequency dispersed whistler emissions and non-dispersed radio pulses. Here, the authors show Jupiter dispersed pulses associated with Jovian lightning that are evidence of low density holes in Jupiter’s ionosphere.